Drug-abusing women have higher rates of pregnancy complications and an increased incidence of infants with lower birth weights and higher rates of congenital malformations and mortality than are seen within the general population. In addition, there is an increased prevalence for longer hospitalization due to neonatal abstinence syndrome. The risk of adverse events in drug-exposed infants can be directly influenced by dose, class of abused substance and time of intrauterine exposure. In addition, poly-drug use may also have an effect on the developmental outcome of the fetus. To better understand the role illicit and licit substances have on the developing fetus, it is necessary that we develop improved methods of detection and gain a better understanding of the transport process involved in the transfer of drug across the placental membrane. Limited data are available correlating the relationships between maternaldrug concentration in plasma, urine, saliva, sweat and hair to amniotic fluid, cord blood, fetal urine, meconium and fetal hair. We have designed several studies to investigate maternal and fetal drug disposition in a variety of biological fluid and tissues. Each maternal specimen provides a history of drug exposure at different stages of gestation. Fetal specimens offer unique information about prenatal drug exposure. Meconium begins to be formed in the 13th week of gestation and hair in the last trimester. Each matrix offers the opportunity to determine if drug concentrations in different matrices relate to maternal and neonatal outcome measures. In addition, due to the low concentrations of drugs in fetal matrices, it is necessary to develop sensitive and selective methods for detecting these compounds. Analytical methods are being improved to offer more sensitive and reliable methods of detecting the parent drug and metabolites of opiates, including buprenorphine and methadone, cocaine, methamphetamine, cannabinoids and nicotine in a variety of maternal and infant specimens. One of the analytical challenges in measurement of drugs following in utero exposure is that drug and metabolite profiles in neonatal specimens may be quite different than those found in adult biological fluids. This may be especially true for premature infants. A major new inititative for us is the quantification of anti-retroviral drugs in meconium in conjunction with the Pediatric HIV/AIDS Cohort Study (PHACS). The Pediatric HIV/AIDS Cohort Study (PHACS) is a longitudinal study, beginning in 2007, assessing occurrences of abnormalities from antiretroviral (ARV) exposure in utero and/or in the first two months of life in multiple domains, including metabolic, growth, cardiac, neurologic, neurodevelopmental, behavior, language, and hearing domains, during infancy and adolescence. Within the PHACS cohort, the Surveillance Monitoring for ARV Toxicities (SMARTT) study is examining clinical and laboratory data from HIV-uninfected children born to HIV-infected women to assess potential signals for adverse events related to gestational ARV exposure. Concerns are being raised about the potential toxicity in some neonates to gestational ARV exposure, including mitochondrial dysfunction, increased bone porosity, and hearing and language impairment. There is a strong need to accurately quantify fetal ARV exposure. We are collaborating with this group to provide meconium ARV measurements of 20 analytes; concentrations in meconium may better predict infants likely to develop ARV-related toxicities. The goal is to determine if meconium ARV analysis better predicts developmental abnormalities than maternal drug history. Currently we are also investigating the utility of ethyl glucuronide, ethyl sulfate and fatty acid ethyl ester concentrations in meconium to detect maternal alcohol consumption during pregnancy. There is great debate in the field about which marker(s) best predict maternal drinking behavior and which marker(s) should be used to screen infants for potential alcohol-related problems. We are collaborating with large clinical studies including PHACS and Prenatal Alcohol in SIDS and Stillbirth (PASS, Safe Passage) study to evaluate these objectives.